The blood-brain barrier (BBB) is a dynamic interface between the blood and the central nervous system (CNS) that controls the influx and efflux of biological substances needed for the brain's metabolic processes, as well as for neuronal function. The BBB comprises specific endothelial cells, brain microvascular endothelial cells (BMECs), which are critical for maintaining homeostasis of the brain microenvironment and neurological health.
In vitro BBB models have been developed to study the molecular mechanisms underlying development of the BBB and to screen for drugs and other chemical compounds that affect BBB integrity. Naik & Cucullo, J Pharm Sci. 2012, 101(4):1337-54; Lippmann et al., Nature Biotechnology 2012, 30:783-791. In order to understand development of the BBB and mechanisms underlying neurological diseases, it is critical to have a renewable source of human BMECs. However, existing methods for differentiating human pluripotent stem cells to BMECs use undefined culture systems that exhibit line-to-line variability, making the methods poorly suited for clinical applications and large scale production. Accordingly, there remains a need in the art for efficient and cost-effective protocols for generating functional brain microvascular endothelial cells under chemically defined culture conditions.